Wednesday, June 08, 2016

Public Release: 6-Apr-2016
Age and mobility predict death better than one's 'molecular clock'
Princeton University, Woodrow Wilson School of Public and International Affairs

Advances in technology allow scientists to measure intricate details about the human body that greatly enhance understanding of health, disease and aging.

Yet, when it comes to predicting death, more rudimentary measures--like a person's age or a person's ability to climb stairs or walk a short distance--are much more powerful predictors of survival than certain biomarkers, according to a study published in PLOS ONE by researchers at Princeton University; Georgetown University; University of Washington; Stanford University; the University of California, Berkeley; and the Universidad de Costa Rica.

Using data from the United States, Costa Rica and Taiwan, the researchers compared a broad set of predictors of death--like age, smoking habits and mobility--with the length of telomeres, DNA sequences that generally shrink with age.

•••••

Telomere length is typically measured in white blood cells (leukocytes), and shorter leukocyte telomeres have been associated with disease, aging and death. For these reasons, there has been great interest in the ability of this biomarker to predict mortality.

After evaluating data, the research team found that using telomere length to predict a human's death was only marginally better than a "coin toss." Chronological age was, by far, the single best predictor of death in all three countries.

•••••

"We were surprised that most indicators outperformed telomere length, including self-reported measures of health and mobility, an assessment of cognitive function, smoking, exercise, an inflammatory marker and a measure of kidney function," said Noreen Goldman, Hughes-Rogers Professor of Demography and Public Affairs at Princeton's Woodrow Wilson School of Public and International Affairs and faculty associate at the Office of Population Research.

"We found that the so-called 'molecular clock' was nowhere near as powerful as the pendulum when it came to predicting five-year mortality--at least among older humans," said co-author Maxine Weinstein, distinguished professor at the Center for Population and Health, Georgetown University.

•••••

Because telomere length is strongly correlated with both age and sex, the researchers next needed to investigate how telomere length fares in predicting mortality after these factors were taken into account. When the researchers controlled for age and sex, they found telomere length ranked near the bottom. It was 15th out of 20 in Costa Rica, and 17th in Taiwan and the U.S. The results show that 13 other indicators could more powerfully predict mortality than telomere length in all three countries.

"To prove its worth, the biomarker 'du jour' should tell us more than we already know based on simpler observables. If mortality prediction is the main goal, telomere length is probably not the best tool," Glei said.

The researchers note some potential limitations of the findings. People who are critically ill might exhibit changes in the distribution of different types of leukocytes that makes their telomeres appear longer. In this study, telomere length is measured in leukocytes, which is common across most research. But some types of leukocytes tend to have longer telomeres than others.

"Telomere length tends to be longer in the type of leukocyte that becomes more dominant when a person is ill. Therefore, a sick person might appear to have 'longer' telomere length, but that is deceptive. In fact, these critically ill individuals may be much more likely to die in the short-term despite the appearance of 'longer' telomeres," Glei said.

It also is plausible that telomere length is a better predictor of long-term mortality, compared to short-term survival, since it reflects the gradual process of cellular aging.

"Alternatively, telomere length might be a predictor of mortality only for certain groups of patients, such as those with cancer," said co-author Rosa Ana Risques, assistant professor of pathology at the University of Washington. "An interesting possibility is that telomere length might not be a good predictor of mortality, but it could be a good predictor of healthy aging. Increasing evidence demonstrates that shorter telomeres are associated with cardiovascular disease, but additional research is needed to clarify the association between telomere length and other diseases of aging such as cancer."

"Another possibility is that change in telomere length might be a more powerful predictor than our measurement, taken at a single time," said Weinstein.

The authors conclude that, while telomere length may eventually help scientists understand aging, it is not as powerful for predicting death over a five-year timespan as other basic, more easily obtained measures--at least among older humans.